Making Health Care Reform "Deficit Neutral" Accomplishes Little--So Why Is That the President's Health Care Reform Budget Objective?

Monday, August 31, 2009
For me, one of the more amazing things about this health care debate is the way the press and many advocates of health care reform have accepted the notion that the fiscal objective should be to pass a health care bill that is "deficit neutral."With health care costs unsustainable, why is that an appropriate goal?Deficit neutral means that any impact of a health care bill on the federal budget

Bob Bennett Wants to Turn "Control of Our Health Insurance System Over to the Government"–-Say What?

Friday, August 28, 2009
That’s what the Club for Growth is saying about Senator Bob Bennett’s health care proposals.Apparently, the Club for Growth has a reading comprehension problem. Or, are they just trying to twist the truth about the Utah Republican's health care efforts? The Wyden-Bennett Healthy Americans Act has to be the most pro-market health care reform proposal on the table.First, it does not have the

The Health Reform Bills Would Be Great For the Business Of Health Care

Thursday, August 27, 2009
Have you noticed how none of the big health care business special interests is running any negative health care reform ads? Why should they when each is poised to gain billions of dollars from it?As President Barack Obama has said many times, any health care bill that costs about $1 trillion would be paid for, roughly half and half, with savings in the health care system and new revenues (taxes).

Health Care Reforms Deeper Problems

Wednesday, August 26, 2009
by BRIAN KLEPPER and DAVID C. KIBBENote: We were asked by Northeast Florida's regional newspaper, the Florida Times-Union, to write a piece for lay audiences distilling our thoughts on what's behind the reform curtain. This piece published this week and, while we doubt much of it will be news to this blog’s readers, we wanted to offer it up as a summary statement.Congress' health care reform

There Will Not Be Health Care Reform in 2009 Without Republican Leadership

Monday, August 24, 2009
I will suggest that there is an opportunity for the Republicans to score a huge political and policy win. It can be done in a bipartisan way and it can be done in a way that does not sell out the core principles that either Republicans or Democrats believe in.It would require a new effort—a clean sheet—this time initiated by the Republicans.The Republicans have won August. No doubt about it. But

Dr. Stephan

After a very challenging summer, I've finally turned in my written thesis, so it's official: I have my Ph.D. I'm publishing the abstract below. These findings should all be published in peer-reviewed journals in the next 6 months.

Ataxin-7 Conserved Motifs Determine the Severity of the Neurodegenerative Disorder Spinocerebellar Ataxia Type 7 in Transgenic Mice and Influence Lifespan in Yeast

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant, progressive neurodegenerative disorder whose characteristic features are cerebellar ataxia, dysarthria, and retinal cone-rod dystrophy culminating in blindness. SCA7 is caused by an abnormally long glutamine-coding CAG repeat in the SCA7 gene, which encodes the protein Ataxin-7.

Ataxin-7 contains several conserved motifs that may influence the toxicity of the glutamine tract. Among these are three conserved regions (conserved block I – III), two caspase-7 cleavage sites, a nuclear export signal and two monopartite nuclear localization signals (NLS). Previous investigations have shown that the caspase-7 cleavage site D266 is required for the full toxicity of the Ataxin-7 protein in cell culture. We generated SCA7 transgenic mice expressing a 92 CAG version of the human SCA7 cDNA, with and without a D266N mutation. Mice carrying the D266N mutation were protected from SCA7-like neurodegeneration, behavioral signs and shortened lifespan.

To further characterize the role of conserved motifs in SCA7 pathology, we generated SCA7 transgenic mice carrying point mutations in both C-terminal NLSs (KKRK -> KAAK). Previous work has shown that nuclear localization is an important step in the pathology of CAG repeat disorders. We observed that mice lacking C-terminal NLS activity were substantially protected from degeneration of the retina and cerebellum, SCA7-like behavioral signs and shortened lifespan.

Age is the primary risk factor for neurodegenerative disease. Even in the absence of overt disease, the aging brain shows histopathological and molecular changes reminiscent of neurodegeneration. To explore the link between neurodegenerative disease and aging, we have examined the replicative lifespan of Saccharomyces cerevisiae missing the SCA7 ortholog, SGF73. This strain exhibits an unusually long lifespan, which is dependent on the function of the NAD+-dependent deacetylase SIR2. We present evidence that the extended lifespan of the SGF73 null strain is due to the influence of Sgf73 on the activity of Sir2 and the histone deubiquitinase Ubp8. Furthermore, we show that the level of ubiquitinated H2B is elevated in an SCA7 transgenic mouse line, indicating that an alteration in Ubp8 activity may play a role in SCA7 pathology and that aging and neurodegeneration may share a common mechanism.

Splitting the Bills? The Democratic Leadership and the White House Staff Really Need a Vacation

Thursday, August 20, 2009
The latest word is that the Democratic leadership and the White House see a “60% chance” they will split their health care bill into two parts—one a budget bill that would be eligible for the 51-vote Senate rule and the other the operational non-budget portions that will need 60 votes. This is all intended to get around the Byrd Rule—which allows the use of reconciliation

FiveFingers in the Alpine Lakes Wilderness

Wednesday, August 19, 2009
I recently bought a pair of Vibram FiveFingers Sprint (pictured). They're minimal, lightweight shoes with "toes". They're designed to mimic barefoot walking as closely as possible, while protecting the feet from punctures and abrasion. The soles are thin, flexible and offer no padding whatsoever.

I've always been a barefoot walker, because our feet evolved to be nude (or close to it). Besides feeling amazing, walking barefoot allows the body to express proper biomechanics. My feet have become tougher over time, but I still can't handle a rough trail barefoot.

When I first put the FiveFingers on, my initial thought was "these don't feel as much like being barefoot as I wish they did". Simply having something between your skin and the ground makes your feet much less sensitive. But I got used to them quickly, eventually using them for my parkour training.

I had a few converstions with my parkour instructor Rafe Kelley, during which I realized I had to re-teach myself how to walk and run correctly. Rafe is well-versed in natural human movement due to his background in MovNat, gymnastics, martial arts, strength training, parkour and anthropology. Modern shoes allow us to walk and run in a way that our bodies did not evolve to tolerate. The padding in shoes allows us to take large steps, in which we overshoot our center of gravity and contact the ground in a jarring manner. It also allows us to strike with our heels when we run, which is not comfortable when you're barefoot.

I took the FiveFingers on a 13-mile hike in the Alpine Lakes wilderness with a few friends last weekend. The Pacific Northwest has to be one of the most beautiful places in the world. I was expecting to use the shoes for a few miles and then swap them for my lightweight hiking shoes (Inov8 Flyroc trail runners). The beginning of the trail was really rocky and I thought I was going to have to take them off in the first few hundred yards. Surprisingly, my feet adapted, and although the trail stayed rocky, it became fairly comfortable by the time we had walked a mile.

I found myself thinking about Rafe's advice, and taking smaller steps that strike closer to my center of gravity. Although my strides were shorter, I had no trouble keeping up, and in fact going up the hills was remarkably easy. We gained 3,000 feet of elevation but I never got winded. I had to pay close attention to foot placement, which kept me from looking around much but was actually kind of fun.

After a few miles, I switched to my hiking shoes, with the idea that I should switch before my feet really started to hurt, rather than after. I immediately noticed that going up hills was harder, especially on my calves. My feet felt more cumbersome as well.

Here's me foraging for mushrooms on the trail. This is Laetiporus sulphureus, also known as "chicken of the woods". It's widely eaten in this area. However, my mushroom guide All That the Rain Primises, and More, had this to say about it:

"If you eat and enjoy this moushroom, always cook it thoroughly and do not serve it to lawyers, landlords, employers, policemen, pit bull owners, or others whose good will you cherish!"

I didn't take my chances. If you're going to pick wild mushrooms, make sure you know what you're doing and carry a regional identification guide. "I recognize them from China/Russia/Europe" kills several people a year in the Pacific Northwest. If you're experienced, this area is a mushroom bonanza. I can't set foot outside without stepping on a king bolete (porcini, cep) in the fall.

I ended up switching back to the FiveFingers for the majority of the hike, about 9 miles of it. The soles of my feet were a bit sore by the end (due to stepping on sharp rocks for miles), but my joints and muscles felt remarkably good! I had no joint pain or muscle tightness. I also felt pretty energetic. This was a big surprise, since I haven't done much hiking this year. The next day, my calves were sore, but that was it.

All in all, I really like the FiveFingers. I can wear them in places that require shoes, yet remain nearly barefoot. One potential drawback is the price-to-durability ratio. They cost me $80 and I don't expect them to last a year. That being said, I'm putting a brutal beating on them. Parkour training destroys shoes. The rubber seems to be excellent quality (which you'd expect from Vibram), but it's thin and it has cuts in it for flexibility and grip, which will lower its lifespan. The upper is simply a piece of stretchy fabric that tears easily. I'm willing to deal with the durability issues because the advantages outweigh them [update- several FiveFingers wearers have commented that they actually last a surprisingly long time. See comments].

The Obama Admistration Would Do Well to Read the Senate Rules and the Polls

The latest reports are that the White House is getting ready to ditch any thoughts about a bipartisan health care bill and just ram the Democratic bills through the Senate with bare majorities. Readers of this blog know that I don’t think it is ever possible to ram anything so big as health care through with slim Congressional majorities and even less public support. I

Co-Ops Are the Single Dumbest Idea I Have Heard in the Health Care Debate in Twenty Years

Monday, August 17, 2009
This is a repost from June 23--sort of like regifting...I am sure you have heard the story about the committee that was charged with designing a horse but, because of the bureaucratic ways of the committee process, instead ended up creating a camel.We will not see a Medicare-like public health plan as part of any health care reform bill in 2009. I know proponents don’t want to hear that but it is

The Other National Universal Systems of Care Are Not Our Problem

You can't have an American health care debate without plenty of trashing of single payer systems elsewhere.I am not a single-payer advocate. I believe it is simplistic to think that if we just had one and eliminated the duplicate expenses multiple payers bring with them everything would be OK.I think a single-payer solution is simplistic because it misses the different histories that have gone on

Ischemic Heart Attacks: Disease of Civilization

Saturday, August 15, 2009
Or, more precisely, disease of industrial civilization.

The scientific literature contains examples of cultures that don't suffer from the chronic non-communicable diseases that are so common in modern societies. Much of what I've read indicates that heart attacks are practically unique to cultures that have adopted industrial foodways and a modern lifestyle, being infrequent or entirely absent in those that have not.

I recently came across an incredible paper from 1964 in the American Journal of Cardiology, titled "Geographic Pathology of Myocardial Infarction", by lead author Dr. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964). This was published during a period of intense research into the cardiovascular health of non-industrial cultures, including Dr. George V. Mann's famous
study of the Masai.

The first thing Lee and his colleagues did was collect autopsy statistics from San Francisco and Los Angeles hospitals. They analyzed the data by race, including categories for Caucasian-Americans (white), Japanese-Americans, Chinese-Americans, and Filipino-Americans. All races had a similar incidence of autopsy-proven myocardial infarction (MI = heart attack), including both silent (healed) and fatal MI. For comparison, they included a table with autopsy data from hospitals in Tokyo, South Japan and North Japan. I'm including the data from Tokyo in the graph because it's also an urban environment, but the finding was the same in all three regions. Here's what they found, by age group:
The Japanese had a very low rate of MI compared to both Caucasian-Americans and Japanese-Americans. The rate of MI in Caucasian-Americans and Japanese-Americans did not differ significantly. Thus, location but not race determined the susceptibility to MI.

Next, the investigators collected autopsy data from hospitals in New Orleans, again divided by race. This time they exained Caucasian-Americans and African-Americans. Both groups had a very high rate of MI, as expected, although the African-Americans had a lower rate than Caucasian-Americans. They also collected data from autopsies in Nigeria and Uganda for comparison. Here are the data for men:
And for women: Again, location but not race largely determined the incidence of MI. MI was extremely rare in the African autopsies. Here's what they had to say:
There was only 1 case of healed myocardial infarction among over 4,000 adult autopsies in the Uganda series, and only 2 cases of healed myocardial infarction among over 500 adult autopsies in the Nigerian series. In the New Orleans Negro series the occurrence rate was far greater in every sex and age group than in either one of the Negro series in East and West Africa.
Over 4,500 autopsies and not a single fatal MI. If this isn't worth studying, what is? These data should be part of first-year training in medicine and health programs.

To satisfy the skeptics, Lee and colleagues imported hundreds of hearts from consecutive autopsies in Albany (USA), Africa, Korea and Japan. They had an American pathologist analyze them side-by side to eliminate any diagnostic bias. Here's what they found:
In the African Negro series no infarct was found in any age group [out of 244 hearts, 39 over 60 years old]. In the Korean series there were only 2 cases of myocardial infarction [out of 106 hearts] and they were both women... In the Japanese series there were 8 cases of myocardial infarction in 259 hearts. All were men...
In the American sample, nearly 40% of the hearts of men and women over 60 showed signs of MI. The findings of the American pathologist confirmed the international autopsy data, showing that diagnostic bias did not contribute to the results significantly. They also took measurements of the thickness of the coronary artery wall, an index of atherosclerosis. They found that the Americans had the most atherosclerosis, but all cultures had some degree of it and there was overlap in the amount of atherosclerosis between samples. This led the investigators to state:
Myocardial infarction and coronary thrombosis are almost nonexistent in Uganda and Nigeria, and the amount of coronary arteriosclerosis is significantly less in Africans than in whites. However, in the two groups there was some overlapping in the degree of arteriosclerosis. No Africans had infarcts, but some had the same or a greater degree of coronary arteriosclerosis as a few whites who had myocardial infarctions. One explanation for this may be that some difference in clotting or clot-lysis mechanisms is present in the two groups. In a previous study, we showed that the incidence of thromboembolic phenomena in the pulmonary circulation [blood clots in the lungs] was low in East Africans as compared with Americans.
Now, the authors' conclusions:
These data strongly suggest that among the Orientals the environmental factor is playing a major role in the etiology of myocardial infarction and coronary thrombosis. If the genetic factor is an important one, those Orientals who moved to this country many years ago or who were born in this country should still maintain their low occurrence rate of myocardial infarction at least to some extent, and one would not expect to see similar occurrence rates of myocardial infarction in Orientals and whites as old as 50 to 59 years... As with the Orientals, this suggests that for Negroes in the United States environmental factors are more important than genetic factors in the etiology of myocardial infarction.
Africans in Africa and Japanese in Japan = low incidence of MI. Africans, Japanese and Caucasians in the US = high and similar incidence of MI. Genes only influence a person's susceptibility to MI when they live in an environment that promotes MI. Otherwise, genes are basically irrelevant.

What do the traditional diets and lifestyles of Japan and Africa have in common? Not much. Even within Nigeria, the diet varies from heavily starch-based (root vegetables, soaked/fermented non-gluten grains, beans, plantains) to mostly reliant on high-fat dairy and meat. In fact, I believe it's the wrong question to ask. A better question is "what do we eat/do in the US that traditional Japanese, Koreans, Chinese, Polynesians, Melanesians and Africans don't"? For starters, none of them rely on industrial vegetable oils, sugar and wheat to nearly the same extent as modern America. Their food is generally prepared at home using wholesome ingredients and traditional methods.

They probably get more exercise than Americans, even if it's only walking in Tokyo or domestic tasks for women in parts of Africa. Traditional Africans surely get more sunlight and thus more vitamin D. I can't imagine life is less stressful in Tokyo than in San Francisco or Los Angeles.

I really like this study, and I think these graphs should be disseminated as much as possible. I've prepared high-resolution versions in JPEG, Powerpoint and PDF formats. E-mail me (click on my profile for the link) if you would like a copy. Let me know which format(s) you want.

Are Democrats Getting Ready to Ditch the Public Option? But They Would Still Be Challenged by the Trillion Dollar Price Tag

It looks to me like the popular objections to a health care bill being expressed by voters this month are concentrated in two primary areas:A concern about “government control of the health care system”—mostly around the public plan option.The trillion-dollar cost of a health care bill at a time deficits are swelling and worries about who will really end up paying for it.As a result of the first

You Call This a Health Care Debate?

Thursday, August 13, 2009
Any of us who do health care policy full time might as well take the rest of the month off and let the demagogues bent on scarring the American people just get it all out. I swear it is getting worse by the hour. Then maybe we can get back to a rational debate.The British Health System's National Institute for Health and Clinical Excellence (NICE) and Dr. Ezekiel Emanuel have been particularly

Cleave and Yudkin on Fats

Wednesday, August 12, 2009
Drs. T. L. Cleave (1906-1983) and John Yudkin (1910-1995) were two diet-health researchers who believed that refined carbohydrate-- and particularly refined sugar-- are behind many modern health problems. They made their case in the scientific journals, as well as in books aimed at the general public. They were also witheringly dismissive of the idea that animal fats could be behind the coronary heart disease epidemic of the 20th century. I'm going to post a few quotes of theirs that I'm particularly fond of, relating to this. I'll start off with a few oldies but goodies from T. L. Cleave's The Saccharine Disease, page 100:
Those who incriminate animal fats in raising the blood lipids and causing coronary disease would have us stop eating the fats that we have been eating from immemorial time, such as the fat found in meat and in the butter and cream derived from milk, and eat instead a whole lot of new oils, mainly expressed from vegetable seeds, many of which oils are alien to us.
From pages 100-101:
The keeping of flocks of sheep, herds of cattle, and other domestic animals, in order to provide a continuity of meat and milk, started with neolithic man many thousands of years before the Christian era... To these fats we are therefore well adapted, quite apart from man, as a hunter, being well acquainted with the fat of animals in evolutionary times far more remote than the neolithic ones.
From page 101:
Contrast with these ancient fats the new oils, mainly expressed from vegetable seeds. Not only are many of these seeds not a natural food for man (e.g., cotton seed and sunflower seed-- and incidentally the sunflower does not even come from the Old World, as we do in the British isles, but from the New), but also the oils expressed from many of them never existed in any quantity before the invention of the modern hydraulic press or the new solvent procedures, and consequently were scarcely eaten in this country before the introduction of margarine, circa 1916, during the First World War. Evolutionarily these oils make us not so much men as the equivalent of a flock of greenfinches, and the evolutionary incongruity is heightened by the fact that the coronary explosion amongst us, as will be seen later, came in since the introduction of just these oils at the period stated, though in margarine they are often saturated by a stream of hydrogen.
Now for a little John Yudkin. From "Dietary Factors in Arteriosclerosis: Sucrose" (Lipids 13(5):370. 1978):
In principle, it is very doubtful that one can in any way profoundly modify the diet of any species, including Homo sapiens, without introducing some hazard. The consumption of large quantities of PUFA [polyunsaturated fat] has been made possible only by the very recent development of sophisticated techniques of cultivating oilseeds, and extracting and refining vegetable oils. Before such techniques were available, these oils made only a small contribution to our diets, as they still do in the poorer countries. We cannot ignore the evidence that the large amounts widely recommended nowadays as a preventive of CHD can produce undesirable effects, such as increasing the risk of gallstones and possibly of carcinomatous changes in the skin. On the other hand, the reduction of the high amounts of sugar that we now consume is not known to be accompanied by any hazard.
Drs. T. L. Cleave and John Yudkin: making sense since 1936.

Why the Democrats Are On Their Way To Blowing Health Care –Again

There will be a pretty long list of answers to this question but I will give you what I consider to be the number one reason.The Democrats chose partisanship over bipartisanship.There has been a school of thought in this town, of which I have strongly agreed with on this blog, that the only way you can do something as big and complicated and close to people’s self interests as health care is to

Insurance Companies Say They Can't Compete With a Public Option--But FedEx and UPS Do Pretty Well Against the Post Office--What's the Difference?

The Post Office doesn’t get to unilaterally fix the cost of all of the things it buys that go into its services--Medicare and Medicaid do.What critics of the public health plan option often fear is that, like Medicare, a public option health plan would be able to unilaterally set what it pays doctors, hospitals, drug companies, and other providers. Private health insurers often pay providers 20%

This Health Care Reform Debate is Really Starting to Scare Me—What if We Were Having a Real One?

Tuesday, August 11, 2009
The recent stridency of this health care debate has led me to wonder what if the Democrats were proposing real health care reform?The Democratic health care bills are hardly more than expansions of the health insurance entitlement paid for by largely insignificant cuts to existing spending and lots of new taxes. Any provider cuts to Medicare are so small they will be easily cost shifted to the

The Bigger the Lie

Monday, August 10, 2009
I come from a corporate background.A longtime ago a chief marketing officer introduced me to the term, “The Big Lie.” Apparently, this also applies to politics.As he put it, in not a complementary way, the bigger the lie that is told the easier it is to believe.Sarah Palin has been practicing Big Lie politics.She recently posted on her Facebook account:“The America I know and love is not one in

Health Insurance Reform or Health Care Reform? The President Gets It Right!

Saturday, August 8, 2009
Advocates of the health care bills now pending in Congress, led by the President, have been calling for health care reform. They argue that our health care system is unsustainable as it is. Not only do we need to create a system of universal coverage but also we need to do it in a way that is sustainable, affordable, and doesn’t continue to add to our deficits.They are right.But, for months I

The Diet-Heart Hypothesis: Oxidized LDL, Part II

In the last post, I presented the evidence that oxidized LDL (oxLDL) is a dominant factor in the arterial disease known as atherosclerosis, although probably not the only factor. In this post, I'll describe some of the major contributors to oxLDL.

Polyunsaturated Fats Increase LDL Oxidation

The serum concentration of oxLDL is strongly influcenced by diet. One dietary determinant of oxLDL is dietary polyunsaturated fat (PUFA). PUFA are inherently susceptible to oxidative damage, compared to monounsaturated and saturated fats. The predominant PUFA in the modern diet is linoleic acid, found excessively in industrial seed oils like corn oil, sunflower oil, safflower oil, cottonseed oil and soy oil. LDL is naturally rich in linoleic acid, even in cultures such as the Kitavans who have a very low dietary intake of it. However, LDL content of linoleic acid does correlate with dietary intake, and the Kitavans have a comparatively small amount of linoleic acid in their LDL, relative to industrial cultures.

There have been a number of media reports in the last few years proclaiming that monounsaturated fat reduces LDL oxidation compared to saturated and polyunsaturated fat. This is rather implausible on the surface, so let's take a closer look. There are two ways to measure oxLDL:
  1. Measure it directly from the blood
  2. Take normal LDL from the blood, expose it to copper in a test tube, and see how fast it oxidizes
The first reflects actual oxLDL in the blood, whereas the second reflects "susceptibility to oxidation" and has a dubious relationship with actual oxidized LDL in the bloodstream. This results in statements like the following (ref):
LDL resistance to copper-induced oxidation, expressed as lag time, was highest during the MUFA-rich diet (55.1±7.3 minutes) and lowest during the PUFA(n-3)– (45.3±7 minutes) and SFA- (45.3±6.4 minutes) rich diets.
This was published in a paper by P. Mata and colleagues in 1996. They fed 42 volunteers one of four different diets for 5 weeks each: one rich in saturated fat, one rich in monounsaturated fat, one rich in linoleic acid PUFA, and one rich in linoleic acid plus omega-3 PUFA. They emphasized the finding quoted above, as did the media. But there's an embarrassing piece of data buried in the paper that the authors, and the media, ignored (thanks to Chris Masterjohn for pointing this out). Here's what they saw when they looked directly at LDL oxidation in their volunteers:

Oops! LDL oxidation in the two PUFA groups was increased by more than 31%. The difference between the leftmost two groups and the rightmost two was statistically significant. As one would expect, oxidized LDL is proportional to the amount of PUFA in LDL, which is proportional to dietary PUFA. This somehow got left out of the abstract and media reports. The same investigators published a similar report a year later.

In another diet trial, participants were placed on one of two diets for 5 weeks: a low-fat, high PUFA diet low in vegetables; or a low-fat, high PUFA diet high in vegetables. The authors were forthright about their findings, so I'll let them summarize:
The median plasma OxLDL-EO6 increased by 27% (P less than 0.01) in response to the low-fat, low-vegetable diet and 19% (P less than 0.01) in response to the low-fat, high-vegetable diet. Also, the Lp(a) concentration was increased by 7% (P less than 0.01) and 9% (P=0.01), respectively.
This is the diet mainstream cardiologists have been prescribing to heart attack patients for 40 years. The trials I mentioned above are the only three I'm aware of in which fat quality was manipulated and oxLDL was directly measured (the first two were based on subsets of the same data). They all suggest that replacing saturated fat with PUFA increases oxLDL.

I suspect that the effect has less to do with the decrease in saturated fat and more to do with the increase in PUFA, although there's no way to know for sure. In the
Lyon Diet-Heart trial, which I believe was the most successful diet trial of all time, linoleic acid was reduced to 3.6% of calories, but saturated fat was also reduced. Another reason is that there are numerous low-fat, low PUFA, high-carbohydrate cultures that have low levels of atherosclerosis and heart attacks. The Kitavans, for example, don't seem to have heart attacks or strokes (although no autopsies have been done so we don't know how much atherosclerosis they have).

They get 69% of their calories from high-glycemic starchy tubers, and their 21% fat comes mostly from coconut so it's highly saturated. Their
blood lipids are low in omega-6 linoleic acid and very saturated. But there's a little surprise in the data: their lipids are full of palmitic acid (saturated), despite the fact that their diet contains very little of it. The reason is that their livers are turning all that carbohydrate into saturated fat, which is what happens when you eat more carbohydrate than you can burn immediately or store as glycogen. The moral of the story is that you don't need to eat saturated fat to have saturated LDL: a high-carbohydrate diet can accomplish the same thing, especially if it has a high glycemic index.

Fat-Soluble Antioxidants Decrease LDL Oxidation

LDL carries fat-soluble antioxidants, predominantly vitamin E and coenzyme Q10 (CoQ10). One form of vitamin E, alpha-tocopherol, slows atherosclerosis in most animal models but has shown equivocal results in human trials. There is even the
suggestion that it may increase LDL oxidation under some circumstances. I don't recommend supplementing with vitamin E. However, the first line of antioxidant defense in LDL is provided by CoQ10. CoQ10 unequivocally reduces LDL oxidation in human subjects, and potently reduces atherosclerosis in animal models.

CoQ10 has a special relationship with cardiovascular health. Levels are reduced in individuals with cardiovascular disease and high oxLDL. Whether this is cause or effect, it's difficult to say. However, supplementing with CoQ10 has been repeatedly shown to be effective for
high blood pressure and congestive heart failure. There has been one controlled trial of CoQ10 (120 mg/day) supplementation for the prevention of heart attacks, which reduced cardiac events including deaths by 45%, compared to a group receiving B vitamins. The CoQ10 group showed a large reduction in plasma lipid oxidation. This is a promising result and the experiment should be repeated.

CoQ10 is not an essential nutrient, although food does contribute a small portion of our total CoQ10 use. The large majority of CoQ10 is synthesized by the body itself, and this is dependent on a number of essential nutrients, including vitamin B2, B3, B5, B6, B12, vitamin C and folic acid. Thus, the body's synthesis of CoQ10 is dependent on overall nutritional status. Sub-clinical deficiency of any of these vitamins can hypothetically contribute to reduced CoQ10 production and thus oxLDL. This is potentially a big problem since modern Americans get more than half their calories from nutrient-poor refined foods.
Liver is the single best source of many of these vitamins, and also holds the title of Most Nutritious Food on the Planet. It's also rich in CoQ10.

CoQ10 synthesis declines with age and is reduced in people with disorders involving oxidative stress, like cardiovascular disease. It's also greatly reduced by the cholesterol-lowering drugs statins. I'm not generally in favor of supplements, but CoQ10 seems to have a lot of promise and nothing but positive side effects that I'm aware of.
CoQ10 deficiency may be a common theme in a number of modern disorders.

Excess Blood Sugar and Fructose Increase LDL Oxidation

type I and type II diabetes are associated with higher levels of oxLDL, therefore, prolonged high blood glucose may contribute to LDL oxidation due to glycosylation of the LDL protein ApoB. Fructose consumption increases oxLDL relative to glucose. Fructose is a very powerful glycosylating agent (binds non-specifically to other molecules, causing damage). Although it isn't present at high levels in the general circulation, it does interact with blood lipids in the hepatic portal vein as it moves from the digestive tract to the liver to be turned into fat (palmitic acid). Peter at Hyperlipid has written extensively about the role of glycosylation in LDL oxidation.

The Diet-Heart Hypothesis: The Verdict

The diet-heart hypothesis, the idea that dietary saturated fat and cholesterol raise blood cholesterol and thus increase heart attack risk, is a half-century embarrassment to the international scientific community. It requires willful ignorance of the fact that saturated fat
does not increase total cholesterol or LDL in humans, in the long term. It requires a simplistic view of blood lipids that ignores the potentially harmful effects of replacing animal fats with carbohydrate or industrial seed oils. Worst of all, it requires selective citation of the literature on diet modification trials.

I have to conclude that if dietary saturated fat and cholesterol play any role whatsoever in cardiovascular disease, it's a minor one that's trumped by other factors. Industrial seed oils and sugar are likely to play an important role in cardiovascular disease.

The Public Plan Option: Litmus Tests Are Never a Good Sign

Thursday, August 6, 2009
Before now, I can think of only one “litmus test” in American politics—abortion.That is an issue that simply polarizes the nation—and our political system. On a good day, people on one side or the other just agree to disagree and move on.But I think we are seeing another litmus test issue emerge—the public health plan option.I have no doubt that there are not the votes to pass a public plan

Never Give Up!

At the rate this crazy health care reform debate is going it could well come full circle and back to twelve Senators who still think they have a good idea--if everyone else would stop digging in on what they can't agree on.This from a Washington Post op-ed they co-authored this week:As 12 U.S. senators from both sides of the aisle who have widely varying philosophies, we offer a concrete

Leave the Town Halls Alone!

Tuesday, August 4, 2009
Apparently, conservative activists are attempting to disrupt town hall meetings being held by Democratic members of Congress to discuss the health care bills.I can tell you from conversations I have had with members of Congress that these town hall meetings are VERY important to representatives and senators of both parties as a way to gauge the mood of their constituents. If activist groups

Finally, A Reasonable Plan for Certification of EHR Technologies

by DAVID C. KIBBE and BRIAN KLEPPERA caution to readers: This post is about methods for certifying Electronic Health Record (EHR) technologies used by physicians, medical practices, and hospitals who hope to qualify for federal incentive payments under the so-called HITECH portion of the American Recovery and Reinvestment Act (ARRA). It may not be as critical as the larger health care reform

The Diet-Heart Hypothesis: Oxidized LDL, Part I

Monday, August 3, 2009
In my reading about lipoprotein particles (LDL, HDL, etc.) and how they associate with cardiac risk, I've come across three LDL-related markers that associate with risk: LDL cholesterol, LDL particle number, and LDL size/density. Is this a coincidence, or is there a reason for it?

The first marker, LDL cholesterol, is probably nothing more than a crude approximation of particle number. But LDL particle number and size/density are related to something else, that probably actually causes atherosclerosis rather than simply being associated with it: oxidized LDL (oxLDL).

oxLDL is formed when the lipids in LDL particles react with oxygen and break down. This happens specifically to the unsaturated fats in LDL, because saturated fats, by their chemical nature, are very resistant to oxidative damage. Polyunsaturated fats are much more susceptible to oxidative damage than saturated or monounsaturated fats. Linoleic acid (the omega-6 fatty acid found abundantly in industrial seed oils) is the main polyunsaturated fatty acid in LDL.

LDL is packaged with antioxidants in the liver, primarily vitamin E and coenzyme Q10 (CoQ10), to prevent its oxidation*. However, the more time it spends in the blood, the more likely it is to exhaust its antioxidant store and become oxidized. Also, the smaller the LDL particle, the more likely it is to become trapped in the vessel wall and become oxidized there.

Oxidized LDL Correlates Tightly with Cardiac Risk

oxLDL has turned out to be a very sensitive marker of cardiac risk, surpassing traditional markers like LDL, HDL, and triglycerides in most studies to date. Since the discovery of sensitive assays that detect oxidized LDL drawn directly from patient blood, a number of studies have been published supporting its ability to detect atherosclerosis (plaque buildup in the arteries), heart attack risk and even the metabolic syndrome.

Holovet and colleagues published a study comparing the ability of oxLDL and a traditional risk factor assessment to detect coronary artery disease. The traditional method is called the Global Risk Factor Assessment Score (GRAS), and includes age, total cholesterol, HDL, blood pressure, diabetes and smoking status. It's similar to the commonly used Framingham risk score (which, interestingly enough, doesn't include LDL).

GRAS was able to correctly differentiate a healthy person from a person with coronary artery disease 49% of the time, while oxLDL was correct 82% of the time. Thus, oxLDL by itself was far more accurate than a whole battery of traditional cholesterol and cardiac markers. Coronary patients had more than twice the level of circulating oxLDL than the healthy comparison group.

In a large prospective study by Meisinger and colleagues, participants with high oxLDL had a 4.25 higher risk of heart attack than patients with lower oxLDL. oxLDL blew away all other blood lipid markers by nearly a factor of two. From the abstract:
Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD.
Oxidized LDL Makes Sense

It's time to cross the threshold from markers of heart attack risk to causes of atherosclerosis. Regular, non-oxidized LDL has few properties that would make it a suspect in atherosclerosis. It's just a little particle carrying cholesterol and fats from the liver to other organs. As soon as it oxidizes, however, it becomes pro-inflammatory, immunogenic, damaging to the vessel wall, and most importantly, capable of transforming immune cells called macrophages into foam cells, a major constituent of arterial plaque.

Researchers have been interested in the plaque-generating properties of oxLDL for over three decades, and quite a bit of data have accumulated. They've identified cellular receptors that allow macrophages to ingest oxLDL (CD36 and SR-A). These receptors are specific for oxLDL and do not recognize normal LDL to a significant degree. Mice whose macrophages lack either of these two receptors have the same amount of circulating LDL as normal mice, yet have 60 to 70 percent less atherosclerosis when fed a plaque-forming diet (1, 2). Shorter-term studies have not always been consistent however, suggesting that there are alternative mechanisms. I'll expand on this more later.

Another line of evidence comes from the ability of LDL-borne antioxidants to prevent atherosclerosis in animal models. The powerful synthetic antioxidant probucol greatly reduces atherosclerosis in a number of animal models. It also reduces the extremely high cholesterol rodents and herbivorous animals get when they eat a high-cholesterol "atherogenic diet", but several studies have concluded that the majority of probucol's effect is due to its antioxidant ability rather than its ability to reduce cholesterol (ref).

Vitamin E and CoQ10 are two other LDL-borne antioxidants that can reduce atherosclerosis in animal models, particularly in combination with one another. Vitamin E alone is not as effective, and in some studies totally ineffective, which is one possible explanation for the equivocal results of vitamin E cardiovascular trials in humans. The most effective combination of antioxidants is probably the one provided by a nutrient-dense diet.

In Summary

Multiple lines of evidence suggest that oxidized LDL plays a dominant role in atherosclerosis. Not only is it associated with cardiovascular risk, there's also a large body of evidence suggesting it actually directly contributes to it. In the next post, I'll describe how you can modify your level of oxidized LDL using diet.

* People often think of colorful fruits and vegetables when they think of antioxidants, but vitamin E and CoQ10 are found in both plant and animal foods. Fruits and vegetables are generally not good sources of these fat-soluble antioxidants. Good sources include organ meats, nuts, pastured butter, avocados and red palm oil. The body also manufactures CoQ10 itself.